Even though the exact etiological mechanisms are not yet known, there is almost universal agreement that Attention-Deficit/Hyperactivity Disorder (ADHD) is a biologically-based disorder, involving impaired self- regulation and producing cognitive, motor, social and behavioral consequences. Evidence-based treatments for ADHD focus on reducing symptoms and impairments of the disorder either through pharmacological means, the use of behavioral therapy, or both. Effects from these treatments are difficult to maintain over time (Jensen et al., 2007), and behavioral treatments are viewed as burdensome to implement by some parents and teachers. Furthermore, despite its established efficacy, pharmacological intervention is controversial in society and is viewed as unacceptable to some families. Thus, the need for additional interventions, particularly those with the potential to offer new options to families and to address ADHD symptoms at the level of brain processes, remains pressing. Towards this end, we pursue an exciting new frontier in ADHD research involving the application of an aerobic physical activity intervention for addressing the disorder, as well as its associated impairments. We approach this goal from an interdisciplinary perspective, combining expertise in neuroscience, kinesiology and both biobehavioral and clinical psychology. Importantly, our preliminary work that is based both on a rodent model of ADHD and on human work with children suggests that aerobic physical activity reduces symptoms characteristic of ADHD. Therefore, we adopt a translational strategy, including both human and animal studies, to address five specific aims: First, we examine the effect of aerobic physical activity on hyperactivity/impulsivity and inattention as well as cognitive, motor, behavioral, and social functioning in young children (ages 5-8 yrs.) and young rats (approximately 40 days old) selected for the presence of ADHD or ADHD-like symptoms, respectively. Second, we examine the minimal length of physical activity intervention required to produce an effect. Third, we examine the persistence of these effects. Fourth, through animal work, we examine the most likely neural plasticity mechanisms that may underlie the effects of physical activity on hyperactivity/impulsivity and inattention through analysis of hippocampal neurogenesis and brain derived neurotrophic factor levels. PUBLIC HEALTH RELEVANCE: There is almost universal agreement that Attention-Deficit/Hyperactivity Disorder (ADHD) is a biologically- based disorder, involving impaired self-regulation and producing cognitive, motor, behavioral, and social consequences. We pursue an exciting new frontier in ADHD research, applying an aerobic physical activity intervention to address the disorder, as well as its associated impairments. We approach this goal from an interdisciplinary perspective, combining expertise in neuroscience, kinesiology, and both biobehavioral and clinical psychology.